Production of a change in the solute permeability of the alveolar epithelium so that it is permeant to macromolecules can be produced by overdistention of areas of the lung in adult and newborn animals with distending forces used clinically to care for respiratory failure in adults and infants. The solute permeability of the alveolar epithelium is measured by comparing the relative rates of loss of several radiolabeled tracer molecules, studied simultaneously, from fetal lung liquid in perinatal animals or from a saline solution instilled into the alveolar space in adult animals. It is planned to study adult sheep, part of whose lung epithelium has been made permeant to proteins by high pressure inflation. Ventilation, blood flow and the development of atelectasis will be determined from dilution of He and loss of N2O during rebreathing. In another group of experiments, the level of left atrial pressure will be elevated by aortic constriction and saline infusion and the left atrial pressure necessary to cause alveolar flooding in lung segments whose epithelium is protein permeant compared to lung segments with a protein impermeant epithelium in the same animal. Perinatal experiments in mature fetal lambs whose fetal lung liquid contains pulmonary surfactant will be subjected to either high pressure ventilation at the onset of breathing or asphyxia and their rate of fetal lung liquid absorption, the protein permeability of their alveolar epithelium, and pattern and effectiveness of gas exchange measured to investigate possible mechanisms of acute lung edema states in newborns. Immature, surfactant deficient lambs will also be investigated using similar measurements to determine if low volume, low pressure ventilation, exogenous administration of surfactant into fetal lung liquid prior to birth, or cholinergic stimulation of surfactant release prior to ventilation will permit a mature pattern of fetal lung liquid absorption and preservation of the normal epithelial impermeability to proteins.